PPP1CA

Chr 11

protein phosphatase 1 catalytic subunit alpha

Also known as: PP-1A, PP1A, PP1alpha, PPP1A

NCBI Gene: 5499 ENSG00000172531 UniProt: P62136 OMIM: 176875

The protein encoded by PPP1CA is the alpha catalytic subunit of protein phosphatase 1 (PP1), a serine/threonine phosphatase that associates with over 200 regulatory proteins to dephosphorylate hundreds of cellular targets involved in cell division, transcription, glycogen metabolism, synaptic plasticity, and circadian rhythm regulation. Mutations cause autosomal dominant neurodevelopmental disorders with intellectual disability, seizures, and multiple organ system involvement. This gene is highly constrained against loss-of-function variants (pLI = 0.99, LOEUF = 0.27), reflecting its essential cellular functions.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is one of the three catalytic subunits of protein phosphatase 1 (PP1). This broadly expressed gene encodes the alpha subunit of the PP1 complex that associates with over 200 regulatory proteins to form holoenzymes which dephosphorylate their biological targets with high specificity. PP1 is a serine/threonine specific protein phosphatase known to be involved in the regulation of a variety of cellular processes, such as cell division, glycogen metabolism, muscle contractility, protein synthesis, and HIV-1 viral transcription. Increased PP1 activity has been observed in the end stage of heart failure. Studies suggest that PP1 is an important regulator of cardiac function and that PP1 deregulation is implicated in diabetes and multiple types of cancer. Three alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2020]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.27

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.27LOEUF

pLI 0.986

Z-score 3.63

OE 0.06 (0.02–0.27)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

3.26Z-score

OE missense 0.36 (0.30–0.44)

75 obs / 207.0 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.06 (0.02–0.27)

0≤0.351.4

Missense OE?0.36 (0.30–0.44)

0≤0.61.4

Synonymous OE?1.16

0≤1.21.6

LoF obs/exp: 1 / 17.3Missense obs/exp: 75 / 207.0Syn Z: -1.20

Background carrier burden — how many people carry a rare variant somewhere in PPP1CA?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 620

328 rare PASS variants

Rare truncating (LoF)

1 in 5,700

48 rare PASS variants

Rare synonymous (reference)

1 in 270

223 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PPP1CA. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 580	1 in 6,600
South Asian	~43k	1 in 450	≈ 1 in 10,000
Remaining (unassigned)	~30k	1 in 960	≈ 1 in 7,500
European (Finnish)	~27k	1 in 1,900	1 in 2,200
Admixed American	~22k	1 in 1,000	≈ 1 in 11,000
African / African American	~21k	1 in 490	≈ 1 in 4,600
East Asian	~20k	1 in 560	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 1,400	≈ 1 in 6,500
Middle Eastern	~2,884	≈ 1 in 580	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 6 of 7 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 7.? see exons ↓